AMP-Activated Protein Kinase Mediates the Effect of Leptin on Avian Autophagy in a Tissue-Specific Manner.
AMP-Activated Protein Kinase Mediates the Effect of Leptin on Avian Autophagy in a Tissue-Specific Manner.
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DOI：
10.3389/fphys.2018.00541
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发表时间：
2018
影响因子：
4
通讯作者：
Dridi S
中科院分区：
文献类型：
--
作者：
Piekarski A;Nagarajan G;Ishola P;Flees J;Greene ES;Kuenzel WJ;Ohkubo T;Maier H;Bottje WG;Cline MA;Dridi S
自噬是一种高度保守的细胞内自我消化过程，在维持细胞内环境稳定中起着不可或缺的作用。虽然新出现的证据表明，内分泌系统调节自噬在哺乳动物中，仍然是一个稀缺的信息在鸟类（非哺乳动物）物种的自噬。在这里，我们表明，脑室内注射瘦素减少摄食量，调节与摄食相关的下丘脑神经肽的表达，激活瘦素受体和信号转导和转录激活因子（Ob-Rb/STAT）途径，并显着增加自噬相关蛋白（Atg 3，Atg 5，Atg 7，beclin 1和LC 3B）在鸡下丘脑，肝脏和肌肉的表达。类似地，瘦素处理激活Ob-Rb/STAT途径，并增加鸡下丘脑器官型培养物、肌肉（QM 7）和肝细胞（Sim-CEL）细胞培养物以及过表达鸡Ob-Rb和STAT 3的中国卵巢（CHO-K1）细胞中自噬相关标志物的表达。为了确定瘦素对自噬作用的下游介质，我们确定了主能量传感器AMP激活的蛋白激酶（AMPK）的作用。瘦素处理显著增加了鸡下丘脑和肝脏中AMPKα1/2磷酸化水平，但对肌肉中AMPK α 1/2磷酸化水平无影响。同样，AMPKα1/2在鸡下丘脑器官型培养物和Sim-CEL中被瘦素激活，但在QM 7细胞中不被激活。通过化合物C阻断AMPK活性逆转瘦素的自噬诱导作用。总之，这些发现表明AMPK以组织特异性方式介导瘦素对鸡自噬的影响。
Autophagy, a highly conserved intracellular self-digestion process, plays an integral role in maintaining cellular homeostasis. Although emerging evidence indicate that the endocrine system regulates autophagy in mammals, there is still a scarcity of information on autophagy in avian (non-mammalian) species. Here, we show that intracerebroventricular administration of leptin reduces feed intake, modulates the expression of feeding-related hypothalamic neuropeptides, activates leptin receptor and signal transducer and activator of transcription (Ob-Rb/STAT) pathway, and significantly increases the expression of autophagy-related proteins (Atg3, Atg5, Atg7, beclin1, and LC3B) in chicken hypothalamus, liver, and muscle. Similarly, leptin treatment activates Ob-Rb/STAT pathway and increased the expression of autophagy-related markers in chicken hypothalamic organotypic cultures, muscle (QM7) and hepatocyte (Sim-CEL) cell cultures as well as in Chinese Hamster Ovary (CHO-K1) cells-overexpressing chicken Ob-Rb and STAT3. To define the downstream mediator(s) of leptin's effects on autophagy, we determined the role of the master energy sensor AMP-activated protein kinase (AMPK). Leptin treatment significantly increased the phosphorylated levels of AMPKα1/2 at Thr172 site in chicken hypothalamus and liver, but not in muscle. Likewise, AMPKα1/2 was activated by leptin in chicken hypothalamic organotypic culture and Sim-CEL, but not in QM7 cells. Blocking AMPK activity by compound C reverses the autophagy-inducing effect of leptin. Together, these findings indicate that AMPK mediates the effect of leptin on chicken autophagy in a tissue-specific manner.
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影响因子：
9.1
作者：
Agrawal, Sudhanshu;Gupta, Sudhir
通讯作者：
Gupta, Sudhir
影响因子：
13.3
作者：
Feng, Yuchen;Backues, Steven K.;Klionsky, Daniel J.
通讯作者：
Klionsky, Daniel J.
DOI：
10.1152/ajpendo.2000.279.1.e116
发表时间：
2000-07-01
影响因子：
5.1
作者：
Dridi, S;Raver, N;Taouis, M
通讯作者：
Taouis, M
影响因子：
19
作者：
Feng, Yuchen;Yao, Zhiyuan;Klionsky, Daniel J.
通讯作者：
Klionsky, Daniel J.
影响因子：
64.8
作者：
Garcia-Prat, Laura;Martinez-Vicente, Marta;Munoz-Canoves, Pura
通讯作者：
Munoz-Canoves, Pura